Soft tissue augmentation is a general term that collectively refers to methods which can be used to diminish the visibility of surface defects in skin, usually including the injection or implantation of some material into the skin of the patient. Injections and implantations can be located at varying depths below the epidermis, including intradermal and subcutaneous (hereinafter generally referred to as “dermal”) depths, depending on the type of defect being treated, the desired effect and material used. Defects such as lines, wrinkles, scars, and the like can be substantially reduced, and in some cases can be made completely unnoticeable, at least temporarily, by such methods.
Soft tissue augmentation can be accomplished in a variety of ways. Two of the more common ways of augmenting soft tissue include the dermal insertion of semi-solid or solid implants of biocompatible materials and the dermal injection of biocompatible materials which may be in the form of a gel or a viscous liquid.
Many substances of varying chemical composition and derivation have been proposed and used as injectable materials for soft tissue augmentation. Materials which have been used in the long history of soft tissue augmentation include silicone products, paraffins, and autologous fat materials. Injectable materials for soft tissue augmentation, which currently seem to be the most widely used, are those which include collagen or are collagen-based. Collagen generally refers to a wide variety of fibrous proteins found in the skin, muscles, tendons, cartilage and bones of animals. Collagen, which usually contains a large amount of proline and hydroxyproline amino acid residues, exists in many triple-helix forms having slightly different physical properties.
There are many factors to be considered when evaluating an injectable material for soft tissue augmentation. These factors fall roughly into four categories which include medical properties, aesthetic properties, practicality and economic considerations. Among the medical properties which a material for soft tissue augmentation should ideally possess are: non-antigenicity, treatment longevity, and stability against migration. Thus, the materials should not cause any reactions in the patient's body, such as erythema, ulceration, inflammation, necrosis, hypo- or hyper-pigmentation, edema, granulomas and/or infection. The materials should cause minimal pain upon injection and should require minimal recuperation time. Aesthetically, the materials should have a natural look and feel to them once inserted into the body. A material which possesses some or all of the preferable medical and aesthetic qualities, should also be practically useful in that a physician can inject it through fine gauge needles with relative ease and withdraw the injection if necessary. Other practical considerations include the shelf life of the material, the storage conditions that the material requires, and the need, if any, for pre-injection preparation. Of course, less pre-injection preparation is preferred. Finally, the overall cost of the material should be considered.
Silicone materials can often be difficult to properly inject for the purposes of soft tissue augmentation.
Autologous fat injections, as well as paraffin injections, have long been known and studied. These materials also have disadvantages. Fat injections can in some circumstances be dangerous and are also very unpredictable with respect to results and treatment longevity. Fat injected into facial lines and wrinkles can cause loss of vision (amaurosis) and even embolism in some patients. Paraffin injections, which are not biocompatible, can result in chronic inflammation and granulomas. Furthermore, some varying portion of a fat injection is usually readily absorbed by the body. Thus, the overall effect of an injected amount of fat is difficult to predict.
Within the last ten to twenty years or so, bovine collagen and, more recently, autologous collagen have become widely used as injectable materials for soft tissue augmentation. However, bovine collagen products can cause allergic responses in patients injected with such materials. It is common to subject a patient to one and sometimes two skin tests using a bovine collagen product as an indicator of potential allergic reaction. Some patients who exhibit negative test results may subsequently develop an allergic reaction, despite such precautionary measures. Autologous collagen obtained from the patient's own body, usually from the patient's skin, and heterologous human collagen obtained from human cadavers have been proposed and implemented as materials for soft tissue augmentation as well. While autologous collagen has reduced the occurrence of allergic responses in some patients, this material also has disadvantages. Autologous collagen is generally produced using the patient's own skin as a starting material. Thus, the starting material is generally obtained by surgical excision of the patient's skin.
Another material which has been proposed for soft tissue augmentation is a gel which contains a cross-linked derivative of a hyaluronic acid. Hyaluronic acid is a high molecular weight polymer having acetylglycosamine and glucuronic acid as alternating units. Hyaluronic acid gels have an advantage over other prior art injectable materials in that they are composed of a polysaccharide which generally produces no adverse immunological effect in the patient. Thus, the adverse reactions are avoided for the most part, as with autologous collagen, but the use of the patient's own skin is avoided. Unfortunately, hyaluronic acid gels suffer from some of the same disadvantages as other prior art materials, particularly decreased longevity due to poor resistance to natural proteases within the patient's body. In general, prior art soft tissue augmentation materials are short-lived and require frequent repetitive injections to maintain skin defect correction levels.
Other gel materials which have been proposed and used for soft tissue augmentation are blood derived gels which are obtainable by withdrawing a patient's blood, combining blood proteins with ascorbic acid (vitamin C) and heat gelling the mixture. While these materials are relatively easy to obtain and cause little, if any, adverse reaction in a patient, they too suffer from a short-lifespan upon injection.
Many different approaches have been taken to increase the longevity of soft tissue augmentation materials by attempting to increase the material's resistance to proteolytic cleavage. Attempts to increase the resistance of prior art injectable materials have generally focused on chemical modification of the materials. Injectable materials containing collagen have been treated with chemical modifiers, such as acylating agents and esterifying agents, in an attempt to increase their proteolytic cleavage resistance. The additional cross-linking of collagen materials and hyaluronic acid has also been suggested for purposes including increasing viscosity and potentially increasing the material's resistance to proteolytic cleavage. Methods which have been proposed for cross-linking collagen materials include thermal, chemical, and irradiation methods. However, the cross-linking of these materials has not resulted in a superior product which is appreciably better in resistance to proteolytic attack by natural enzymes. At any rate, prior art injectable materials for soft tissue augmentation have often failed to satisfy many of the desired characteristics sought in such a material.
Therefore, there still exists a need in the art for safe, non-antigenic, non-irritating, longer-lasting and aesthetically-pleasing injectable materials for soft tissue augmentation which are relatively easy to obtain and/or manufacture.